Once-daily, Single-tablet Regimen Takes Center Stage at CROI

Not long ago, the Janssen Pharmaceutical Companies of Johnson & Johnson unveiled analyses from pivotal Phase 3 trials of its investigational, complete, once-daily, single-tablet regimen of darunavir 800mg/cobicistat 150mg/emtricitabine 200mg/tenofovir alafenamide 10mg (D/C/F/TAF.) These analyses were presented at the annual Conference on Retroviruses and Opportunistic Infections (CROI) in Boston on Monday, March 5, to an eager body of scientists and advocates.

Kimberley Brown, PharmD, AAHIVE, is Medical Director, HIV of Janssen Scientific Affairs, A Pharmaceutical Company of Johnson & Johnson. While many of us go about our daily run-of-the-mill professional lives, Brown keeps herself busy — by developing ways to extend and improve the quality of life for people living with HIV.

Medical science, admittedly, can only go so far, while the bulk of responsibility lies with the person infected with HIV. Adherence, Brown deliniated, is the key to effective HIV drug regimens.

“Despite significant progress, clinical challenges remain in the management of HIV related to adherence and the risk of developing HIV drug resistance,” Brown told HIV Plus Magazine. “In the treatment of HIV, adherence is critical, because missing just a few doses can lead to drug resistance, which can stop a person’s medication from working.  However, people living with HIV often miss doses of their treatment due to a variety of factors, including pill burden, convenience, stigma and tolerability of therapy over time.”

Many of the most common detrimental side effects from combination drug therapies include bone density and kidney-related problems. The end-goal is to minimize these problems. “If approved in the U.S.,” Brown explained, “D/C/F/TAF could give clinicians a simplified treatment option that offers the benefit of a once-daily STR with the durability and high barrier to resistance of darunavir coupled with the bone and renal safety profile of TAF for those living with HIV who may be at risk for drug resistance.”

A new drug application (NDA) for D/C/F/TAF was filed on September 22, 2017 to the U.S. Food and Drug Administration (FDA), Brown said, and is currently under review. The NDA was filed for the treatment of HIV-1 infection in adults and pediatric patients ages 12 and older and was based on the results from the EMERALD and AMBER Phase 3 pivotal trials studies.

“The EMERALD and AMBER trials demonstrate the potential of D/C/F/TAF as an important treatment option for a wide-range of patients regardless of previous treatment history, including those with previous virologic failure, experience with multiple ARVs, and in some cases, unknown baseline RAMs to agents other than study drugs,” Brown explained. “The post-hoc analyses presented at CROI are consistent with the pivotal data previously presented and are relevant to the real-life clinical challenges physicians face in treating diverse patients with different levels of treatment experience.”

If approved, the drug would be the only complete regimen that would deliver the benefit of a once-daily STR with the “durability and high barrier to resistance of darunavir coupled with the bone and renal safety profile of TAF.” 

In her own opinion, the most exciting takeaway is that these analyses are uniquely relevant to the real-life clinical challenges that physicians face in treating a diverse range of patients, in the traditional sense but also in the standpoint of different levels of treatment experience. “Unlike other HIV switch studies,” Brown said, “EMERALD had more inclusive entry criteria and may be more representative of the treatment-experienced patients in clinical practice since the study included patients with previous non-darunavir virologic failure, prior experience with multiple antiretroviral and known baseline resistance-associated mutations to agents other than study drugs. Yet, we will saw high response rates and low rebound rates in both our pivotal trials even with this more inclusive criteria.”

These analyses demonstrate the potential of the drug candidate as an important treatment option for patients regardless of previous treatment history. Brown assured us that Janssen remains committed to developing a range of treatment options that address real-world clinical and disease challenges and diverse patient needs.